The proposed research will test the utility in clinical psychiatric applications of a newly- developed method for measurement of the hormone cortisol. The new method uses an ultraminiature device, installed in the mouth of a subject, to continuously accumulate cortisol from the saliva. The rate of accumulation at any moment directly reflects the availability of this hormone to tissue. The total accumulation over some time (1 to 10 h) reflects the time integral of cortisol availability to tissue. This is advantageous since cortisol levels in the circulation and in the saliva fluctuate widely over short time intervals, and less than 10% of cortisol in blood is actually available to tissue. The new method represents both the most direct and the least invasive way of determining the actual degree of tissue exposure to cortisol. Brain hyperexposure to cortisol is implicated in the etiology of some forms of depression, and is thought to accompany sleep disorders, cognitive deficits, and psychotic features of depression. Further, abnormalities of cortisol regulation occur in a state-dependent way in depression, so that monitoring cortisol regulation regularly may allow prediction of the clinical course of the disease. If the new method proves to have diagnostic or predictive utility in psychiatry, widespread clinical use and commercial success are expected.